Research Progress on Metabolite Identification of Synthetic Cannabinoid New Psychoactive Substances / 法医学杂志

Synthetic cannabinoids are currently a class of new psychoactive substances with the largest variety and most abused. Metabolite identification research can provide basic data for monitoring synthetic cannabinoids abuse, which is the current research hotspot. The main trend of structural modification of synthetic cannabinoid is to replace the fluorine atom on pentyl indole or indazole cyclopentyl with hydrogen atom, which greatly improves the biological activity of the compound. The main metabolic reactions include hydroxylation, fluoropentyl oxidative, ester hydrolyze, amide hydrolysis. Liquid chromatography-high resolution mass spectrometry has become the preferred choice for the structural identification of metabolites. This review mainly summarizes research on metabolism software prediction and human hepatocyte model, human liver microsomes model, rat in vivo model, zebrafish model and fungus C. elegans model in metabolite identification based on the structure and classification of synthetic cannabinoids.

Quality consistency evaluation and intelligent visualization of performance parameters of carboxymethylcellulose sodium / 药学学报

In this study, physical fingerprint and multivariate statistical analysis was applied to characterize the quality consistency of different sources of carboxymethylcellulose sodium, and the visualization of R language was used to explore the intrinsic correlation on its performances, and we drew contour maps between independent variables and flowability of powder to find the design space. Through the physical fingerprint and multivariate statistical analysis, it was found that there were differences in the powder properties of carboxymethylcellulose sodium from different sources, and its moisture content, bulk density and tapped density have a great influence on the fluidity. The fillibility was positively correlated with flowability, both negatively correlated with compressibility by R intelligent visualization analysis, which was statistically significant (P < 0.01). When the angle of repose is 30° - 40°, the appropriate design space was found as 5.092 2% < moisture content < 7.006 7%, 0.560 2 g·cm-3 < bulk density < 0.579 9 g·cm-3, and 0.646 3 g·cm-3 < tapped density < 0.816 5 g·cm-3. The results show that it is scientific and feasible to evaluate the quality consistency of pharmaceutical excipients by using the physical fingerprint, multivariate statistical analysis and visualization methods, which provides new ideas for the production and quality evaluation of excipients and the development of generic prescriptions.

The determination of diflucortolone in rabbit plasma by liquid chromatography-tandem mass spectrometry (LC-MS/MS) / 药学学报

A sensitive and efficient liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for quantitative determination of diflucortolone in rabbit plasma after dermal administration of diflucortolone valerate cream to rabbits. After extraction with ethyl acetate, the chromatographic separation was performed on Zorbax Eclipse XDB-C18 (50 mm×4.6 mm, 5 μm) with a gradient mobile phase consisting of 50% acetonitrile-50% methanol and 0.1% formic acid-5% methanol-5 mmol·L-1 ammonium formate at a flow rate of 0.35 mL·min-1. The quantitative analysis was carried out using multiple reaction monitoring (MRM) at specific ion transitions of m/z [M+H]+ 395.2→m/z 355.2 for diflucortolone and m/z [M+H]+ 258.1→m/z 120.9 for ethoxyphenylethylamine (internal standard) in positive ion mode with electrospray ionization (ESI) source. This validated LC-MS/MS method had a linearity over the concentration range of 0.01-10 ng·mL-1 with the lower limit of quantification (LLOQ) at 0.01 ng·mL-1. At level of LLOQ, the inter and intra-assay precision (RSD) were no greater than 9.82% and 11.0%, respectively. The main pharmacokinetic parameters of the diflucortolone including tmax, Cmax, AUC0-72 h, and t1/2 were as follows: (6.33±1.21) h, (0.168±0.080 0) ng·mL-1, (3.15±0.834) h·ng·mL-1, (32.0±17.4) h. The method was validated in the pharmacokinetic study of diflucortolone in rabbit following dermal administration of diflucortolone valerate cream at dose of 0.01 g·cm-2. In this study, the program of animal testing had been approved by Committee on the management and usage of experimental animal in the Evaluation Company of Innovative Drug, Tianjin Institute of Pharmaceutical Research.

In vitro-in vivo correlation of goserelin acetate microspheres / 药学学报

The objective of this paper was to establish a level A in vitro-in vivo correlation (IVIVC) for goserelin acetate extended release microspheres for injection. Three kinds of goserelin acetate microspheres with different release rates were prepared and the critical physicochemical properties, such as drug loading, particle size, glass transition temperature and morphology were characterized. In vitro dissolution test of the prepared goserelin acetate microspheres was performed using sample-and-separate method at 45 ℃ in 5% (v/v) methanol. The morphology of the microspheres and the molecular weight of poly (lactic-co-glycolic acid) (PLGA) of the prepared goserelin acetate microspheres were investigated to research the release mechanism of microspheres. The plasma concentration of goserelin was detected after intramuscular injection of goserelin acetate microspheres to SD rats, and correlated with the in vitro release profiles after processing by percent AUC method. The pharmacokinetic experimental protocol of goserelin acetate microspheres for injection in SD rats was approved by the Animal Ethics Committee of Shandong Luye Pharmaceutical Co., Ltd. The results indicated that the developed sample and separate method was able to detect differences in the release characteristics of the prepared goserelin acetate microspheres, and the in vitro-in vivo correlation of goserelin acetate microspheres was excellent (r > 0.98) and had good predictive ability in SD rats.

Classification of Cimicifuga species based on 1H-NMR fingerprint combined with pattern recognition technique / 中国中药杂志

The metabolomic analysis of three Cimicifuga species was performed using H-NMR spectroscopy and pattern recognition (PR) techniques. A broad range of metabolites could be detected by 'H-NMR spectroscopy without any chromatographic separation. The analysis using principal component analysis (PCA) and discriminant partial least square (DPLS) of the 1H-NMR spectrum showed a clear discrimination between C. foetida and the other two species. The major metabolites responsible for the discrimination were triterpenoid saponins and saccharides. These results indicated that the combination of 1H-NMR and PR provides a useful tool for chemotaxonomic analysis and authentification of Cimicifuga species, and could used for the quality control of plant materials.